Over 60% of adults age ? 65 years have high blood pressure (BP), but optimal management of high BP in the elderly remains controversial. Contrary to evidence in middle age that lowering BP is clearly beneficial, data in older adults are inconsistent and high BP may not be a risk factor in all elders. We recently reported that, among participants in the National Health and Nutrition Examination Survey age e65 years, high BP was a risk factor for all-cause and cardiovascular (CV) death only among persons in better health status (defined as fast walking of a 20-ft walk test). In contrast, high BP was not a risk factor among slow walkers. Additionally, the benefit of lowering BP in all elders remains an issue of debate; a recent meta-analysis in persons age 80 years and older reported no benefit of BP treatment on mortality, and significant heterogeneity across trials. Finally, there is growin concern for potential harms associated with treatment to lower BP. Excessive lowering of BP, particularly diastolic, has been associated with increased risk for death and cardiovascular events in some studies. In the proposed research, we propose a novel paradigm where the associations of BP with adverse outcomes in older persons are considered in the setting of the complex aging process. Our long-term goal is to reliably identify elderly persons in whom BP treatment is beneficial and those in whom treatment is ineffective or even harmful, by defining subpopulations of similar health status. Specifically, aim 1 proposes to elucidate factors from four domains (functional, cognitive/mental, self-rated health, and physiologic) that can identify elderly persons in whom high systolic BP is strongly associated with higher risk for death and CV events, and those in whom it is not, using data from three NIH-funded cohorts: Cardiovascular Health Study (CHS), Health Aging and Body Composition (Health ABC) and Sacramento Area Latino Study of Aging (SALSA). In aim 2, we will evaluate the role of diastolic BP across level of health status. Finally, based on findings from these observational cohorts, in aim 3 we will evaluate whether these factors can identify elderly persons in whom treatment to lower BP is of maximum benefit in two randomized controlled trials: the Systolic Hypertension in the Elderly (SHEP) and the Secondary Prevention of Small Subcortical Strokes (SPS3). Since participants in trials are healthier than the U.S. population, we will also evaluate the effect of treatment in the observational studies, using state-of-the-art causal inference methods, which can correct for the bias of standard analytic approaches. Completion of these aims will substantially advance our understanding of the importance of high BP in older adults; will improve our ability to identify elderly persons who will benefit from BP treatment; will allow a systematic understanding of groups in whom evidence for BP treatment is lacking; and will guide design of future trials of hypertension in elderly adults.